Expression and Regulation of the PD-L1 Immunoinhibitory Molecule on Microvascular Endothelial Cells

Eppihimer, Michael J.; Gunn, Jason R.; Freeman, Gordon J.; Greenfield, Edward; Chernova, Tetyana; Erickson, Jon W.; Leonard, John P.

doi:10.1038/sj.mn.7800123

Cited by 106 publications

(121 citation statements)

References 15 publications

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“…Consistent with our findings, IL-12 has been shown to regulated B7-H1 expression via IFN-γ in other cell types (Eppihimer et al, 2002;Cheng et al, 2007). Studies have suggested that B7-H1 expression was significantly increased on microvascular endothelial cells in vitro and in vivo after IL-12-challenge, but IL-12 was not effective at inducing B7-H1 expression in tissues of IFN-γ-deficient mice.…”

Section: Discussionsupporting

confidence: 90%

“…Studies have suggested that B7-H1 expression was significantly increased on microvascular endothelial cells in vitro and in vivo after IL-12-challenge, but IL-12 was not effective at inducing B7-H1 expression in tissues of IFN-γ-deficient mice. These data showed that elevation of B7-H1 expression was induced by IL-12 through IFN-γ (Eppihimer et al, 2002). Comparable and similar data were observed in EAE mice.…”

Section: Discussionsupporting

confidence: 81%

See 1 more Smart Citation

IL-12 Regulates B7-H1 Expression in Ovarian Cancer-associated Macrophages by Effects on NF-κB Signalling

Xiong¹,

Ma²,

Wu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 81%

IL-12 Regulates B7-H1 Expression in Ovarian Cancer-associated Macrophages by Effects on NF-κB Signalling

Xiong¹,

Ma²,

Wu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…The expression of PD-L1 on VECs has been related to the negative regulation of T cells. 17,18 In this study, we demonstrate that VECs not only express PD-L1, but also B7-1 (CD80), one of its receptors. The interaction between PD-1 and PD-L1 is well established as playing a vital role in controlling T-cell responses in a variety of contexts, from development to autoimmunity to microbial pathogenesis to tumor immunity.…”

Section: Discussionmentioning

confidence: 52%

“…15,16 Interestingly, PD-L1 also has been reported to be present on VECs under basal conditions, and the surface expression of PD-L1 on VECs can be increased by interferon-␣, -␤, and -␥. 17,18 However, the anti-angiogenic effect of PD-L1 has not been demonstrated to date. Here, we provide evidence for a novel regulatory function for PD-L1 in VEC proliferation in vitro and corneal angiogenesis in vivo.…”

mentioning

confidence: 99%

A Novel Function for Programmed Death Ligand-1

Jin

Chauhan

Annan

et al. 2011

The American Journal of Pathology

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Programmed death ligand-1 (PD-L1) plays a critical role in T-cell regulatory function. Here, we report a newly discovered effect of PD-L1 on angiogenesis. We demonstrate that PD-L1 and its receptor CD80, but not PD-1, are expressed by primary murine lung and heart vascular endothelial cells and the miscrovascular endothelial cell line (MS1) at both the mRNA and protein levels in vitro. The inhibition of PD-L1 or CD80 expression in MS1 cells, by small-interfering RNA transfection, led to a significant up-regulation of vascular endothelial growth factor receptor 2 expression and cell proliferation levels in MS1 cells. Furthermore, MS1 cells were found to have a significantly lower proliferation and vascular endothelial growth factor receptor 2 expression levels when they were co-cultured with PD-L1-expressing normal corneal epithelial cells, as compared to MS1 cells co-cultured with PD-L1 ؊/؊ corneal epithelial cells. In a sutureinduced corneal angiogenesis model, we observed a significantly higher level of angiogenic response in PD-L1 ؊/؊ knockout mice as compared to wild-type mice, although there was no significant difference in the expression of inflammatory cytokines (interleukin-1␣, interleukin-1␤, or tumor necrosis factor-␣) or the infiltration of innate immune cells (neutrophils and macrophages) between the two groups. We conclude that the expression of PD-L1 in both vascular endothelial cells and corneal epithelial cells regulates corneal angiogenesis.

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“…PD-1 has two known ligands: PD ligand (PD-L)1 (B7-H1) and PD-L2 (B7-DC). PD-L1 is expressed in a wide variety of tissues and by a number of different cell types, and its expression is upregulated by IFN-␥ (13)(14)(15)(16)(17)(18)(19). The expression of PD-L2 is much more restricted and appears to be limited to a subset of bone marrow-derived cells, including dendritic cells and macrophages (15,20).…”

Section: Pd-1:pd-l1 Interactionsmentioning

confidence: 99%

PD-1:PD-L1 Interactions Contribute to the Functional Suppression of Virus-Specific CD8+ T Lymphocytes in the Liver

Maier

Isogawa

Freeman

et al. 2007

The Journal of Immunology

219

172

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Mechanisms contributing to the development of chronic viral infections, including chronic hepatitis B virus (HBV) infections, are not well understood. We have shown recently that production of IFN-γ, an important antiviral cytokine, by HBV-specific CTLs is rapidly induced when they enter the liver of HBV transgenic mice, and then rapidly suppressed, despite the continued presence of Ag. Suppression of IFN-γ production by the CTLs coincides with the up-regulation of programmed cell death (PD)-1, a cell surface signaling molecule known to inhibit T cell function. To determine whether PD-1 plays a role in the functional suppression of IFN-γ secretion by CTLs, we treated HBV transgenic mice with blocking Abs specific for PD ligand (PD-L)1, the most widely expressed PD-1 ligand, and adoptively transferred HBV-specific CTLs. Treatment with anti-PD-L1 Abs resulted in a delay in the suppression of IFN-γ-producing CTLs and a concomitant increase in the absolute number of IFN-γ-producing CTLs in the liver. These results indicate that PD-1:PD-L1 interactions contribute to the suppression of IFN-γ secretion observed following Ag recognition in the liver. Blockade of inhibitory pathways such as PD-1:PD-L1 may reverse viral persistence and chronic infection in cases in which the CTL response is suppressed by this mechanism.

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Expression and Regulation of the PD-L1 Immunoinhibitory Molecule on Microvascular Endothelial Cells

Abstract: These data show the expression of a novel B7-like molecule on murine ECs that is mediated by IFN-alpha, -beta, and -gamma, and suggest a potential pathway by which ECs may modulate T-cell function.

Cited by 106 publications

References 15 publications

IL-12 Regulates B7-H1 Expression in Ovarian Cancer-associated Macrophages by Effects on NF-κB Signalling

IL-12 Regulates B7-H1 Expression in Ovarian Cancer-associated Macrophages by Effects on NF-κB Signalling

A Novel Function for Programmed Death Ligand-1

PD-1:PD-L1 Interactions Contribute to the Functional Suppression of Virus-Specific CD8+ T Lymphocytes in the Liver

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